Loss of Transient Receptor Potential Melastatin 3 ion channel function in natural killer cells from CFS/ME (2018) Cabanas, Marshall-Gradisnik et al

hixxy · Aug 24, 2018

Mol Med. 2018 Aug 14;24(1):44. doi: 10.1186/s10020-018-0046-1.

Loss of Transient Receptor Potential Melastatin 3 ion channel function in natural killer cells from Chronic Fatigue Syndrome/Myalgic Encephalomyelitis patients.

Cabanas H, Muraki K, Eaton N, Balinas C, Staines D, Marshall-Gradisnik S.

Abstract

BACKGROUND:
Chronic Fatigue Syndrome (CFS)/ Myalgic Encephalomyelitis (ME) is a debilitating disorder that is accompanied by reduced cytotoxic activity in natural killer (NK) cells. NK cells are an essential innate immune cell, responsible for recognising and inducing apoptosis of tumour and virus infected cells. Calcium is an essential component in mediating this cellular function. Transient Receptor Potential Melastatin 3 (TRPM3) cation channels have an important regulatory role in mediating calcium influx to help maintain cellular homeostasis. Several single nucleotide polymorphisms have been reported in TRPM3 genes from isolated peripheral blood mononuclear cells, NK and B cells in patients with CFS/ME and have been proposed to correlate with illness presentation. Moreover, a significant reduction in both TRPM3 surface expression and intracellular calcium mobilisation in NK cells has been found in CFS/ME patients compared with healthy controls. Despite the functional importance of TRPM3, little is known about the ion channel function in NK cells and the epiphenomenon of CFS/ME. The objective of the present study was to characterise the TRPM3 ion channel function in NK cells from CFS/ME patients in comparison with healthy controls using whole cell patch-clamp techniques.

METHODS:
NK cells were isolated from 12 age- and sex-matched healthy controls and CFS patients. Whole cell electrophysiology recording has been used to assess TRPM3 ion channel activity after modulation with pregnenolone sulfate and ononetin.

RESULTS:
We report a significant reduction in amplitude of TRPM3 current after pregnenolone sulfate stimulation in isolated NK cells from CFS/ME patients compared with healthy controls. In addition, we found pregnenolone sulfate-evoked ionic currents through TRPM3 channels were significantly modulated by ononetin in isolated NK cells from healthy controls compared with CFS/ME patients.

CONCLUSIONS:
TRPM3 activity is impaired in CFS/ME patients suggesting changes in intracellular Ca2+ concentration, which may impact NK cellular functions. This investigation further helps to understand the intracellular-mediated roles in NK cells and confirm the potential role of TRPM3 ion channels in the aetiology and pathomechanism of CFS/ME.

KEYWORDS:
Calcium; Chronic fatigue syndrome/Myalgic encephalomyelitis; Flow cytometry; Natural killer cells; Patch-clamp; Transient receptor potential Melastatin 3
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https://www.ncbi.nlm.nih.gov/pubmed/30134818
https://molmed.biomedcentral.com/articles/10.1186/s10020-018-0046-1

hixxy · Aug 24, 2018

I thought this had been posted already but I couldn't find it. Maybe it was just an early announcement I saw.

John Mac · Aug 24, 2018

It was mentioned in a Facebook post discussed here:

https://www.s4me.info/threads/don-staines-and-griffith.5233/#post-94625

Londinium · Aug 24, 2018

Interesting result and clear the NCNED team are still pursuing their calcium theory. However (as the limitations section notes), this had only six patients and six controls so, even though it found statistically significant differences between patients and controls, it is in dire need of replication before drawing too much in the way of conclusions. *If* replicated then it would seem to provide a potential explanation for the reduced NK-cell function that has been reported multiple times in ME/CFS studies.

Sly Saint · Dec 26, 2019

TRPM3 transient receptor potential cation channel subfamily M member 3 [ Homo sapiens (human) ]
Gene ID: 80036, updated on 20-Dec-2019

https://www.ncbi.nlm.nih.gov/gene/80036

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